iProXProteomicsDebing XiangHomo Sapienshttp://www.iprox.org/page/project.html?id=IPX0017559000xdb86@cqu.edu.cnJiangjin Hospital of Chongqing UniversityiProXfalseECM1/SQSTM1 Axis Remodels Colorectal Cancer Immune Microenvironment via CXCL1-CXCR2-Dependent Neutrophil Recruitment and NETosisIn this study, we demonstrate that ECM1 derived from intestinal epithelial cells (IECs) serves as a critical driver of CRC progression. The deficiency of Ecm1 specifically in intestinal epithelial significantly suppresses both colitis-associated and spontaneous colorectal tumorigenesis in vivo. Through single-cell and spatial transcriptomic analyses, we reveal that ECM1 regulates neutrophil recruitment and activation within the tumor microenvironment (TME). Mechanistically, ECM1 functions as a scaffold protein that facilitates the interaction between SQSTM1 and RIP1, thereby initiating NF-κB-meditated CXCL1 secretion. This signaling pathway recruits neutrophils and induces the formation of neutrophils extracellular traps (NETs), creating an immune barrier that excludes CD8+ T cells. Notably, targeting ECM1 effectively mitigates neutrophil-mediated immunosuppression and reverses anti-PD-1 immunotherapy resistance in subcutaneous tumor-bearing mice.Mon Jun 01 00:00:00 BST 2026PXD0791139606